Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements.

PURPOSE: The purpose of this study is to use dynamic [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO2) measurements. PROCEDURES: BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO2 measurements. Data from 120-min dynamic [18F]FMISO scans were fit to two-compartment irreversible three rate constant (K 1, k 2, k 3) and Patlak models (K i). Tumor HFs were calculated and compared using K i, k 3, TBR, and pO2 values. The clinical impact of each method was evaluated on [18F]FMISO scans for three non-small cell lung cancer (NSCLC) radiotherapy patients. RESULTS: HFs defined by TBR (≥1.2, ≥1.3, and ≥1.4) ranged from 2 to 85 % of absolute tumor volume. HFs defined by K i (>0.004 ml min cm-3) and k 3 (>0.008 min-1) varied from 9 to 85 %. HF quantification was highly dependent on metric (TBR, k 3, or K i) and threshold. HFs quantified on human [18F]FMISO scans varied from 38 to 67, 0 to 14, and 0.1 to 27 %, for each patient, respectively, using TBR, k 3, and K i metrics. CONCLUSIONS: [18F]FMISO PET imaging metric choice and threshold impacts hypoxia quantification reliability. Our results suggest that tracer kinetic modeling has the potential to improve hypoxia quantification clinically as it may provide a stronger correlation with direct pO2 measurements.

Role of chitinase 3-like-1 and semaphorin 7a in pulmonary melanoma metastasis.

The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its ß1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis.

Tumor-associated mutations in O6 -methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality.

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6 -methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6 -benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

Fenbendazole as a potential anticancer drug.

BACKGROUND/AIMS: To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. MATERIALS AND METHODS: We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. RESULTS: Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. CONCLUSION: These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation.

A prospective, multicenter study of complementary/alternative medicine (CAM) utilization during definitive radiation for breast cancer.

PURPOSE: Although complementary and alternative medicine (CAM) utilization in breast cancer patients is reported to be high, there are few data on CAM practices in breast patients specifically during radiation. This prospective, multi-institutional study was conducted to define CAM utilization in breast cancer during definitive radiation. MATERIALS/METHODS: A validated CAM instrument with a self-skin assessment was administered to 360 Stage 0-III breast cancer patients from 5 centers during the last week of radiation. All data were analyzed to detect significant differences between users/nonusers. RESULTS: CAM usage was reported in 54% of the study cohort (n=194/360). Of CAM users, 71% reported activity-based CAM (eg, Reiki, meditation), 26% topical CAM, and 45% oral CAM. Only 16% received advice/counseling from naturopathic/homeopathic/medical professionals before initiating CAM. CAM use significantly correlated with higher education level (P<.001), inversely correlated with concomitant hormone/radiation therapy use (P=.010), with a trend toward greater use in younger patients (P=.066). On multivariate analysis, level of education (OR: 6.821, 95% CI: 2.307-20.168, P<.001) and hormones/radiation therapy (OR: 0.573, 95% CI: 0.347-0.949, P=.031) independently predicted for CAM use. Significantly lower skin toxicity scores were reported in CAM users vs nonusers, respectively (mild: 34% vs 25%, severe: 17% vs 29%, P=.017). CONCLUSION: This is the first prospective study to assess CAM practices in breast patients during radiation, with definition of these practices as the first step for future investigation of CAM/radiation interactions. These results should alert radiation oncologists that a large percentage of breast cancer patients use CAM during radiation without disclosure or consideration for potential interactions, and should encourage increased awareness, communication, and documentation of CAM practices in patients undergoing radiation treatment for breast cancer.

Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy.

OBJECTIVE: Abdominal and pelvic radiotherapy is limited by the radiosensitivity of the small and large intestine. PHY906 (KD018), a state-of-the-art, well defined adaptation of a traditional Chinese medicine, decreased intestinal injury from chemotherapy in preclinical studies and is in clinical trials with chemotherapy. This project assessed whether PHY906 would also reduce intestinal injury from abdominal irradiation in mice. MATERIALS AND METHODS: BALB/c mice received whole-abdomen irradiation (2 Gy/day) ± PHY906 by oral gavage twice daily for 4 days. Intestinal injury was assayed by physiological observations and histological studies. Effects of PHY906 on EMT6 mouse mammary tumors were assayed in tumor growth studies. RESULTS: PHY906 decreased toxicity from fractionated abdominal irradiation. Radiation alone produced marked blunting and loss of villi, crypt hyperplasia and irregular crypt morphology, which were reduced by PHY906. The radiation-induced reduction in viable crypt numbers was also mitigated by PHY906. PHY906 did not alter radiation-induced weight loss, but resulted in more rapid recovery. PHY906 did not alter tumor growth, local invasion or metastatic spread and did not protect tumors from growth delays produced by single-dose or fractionated irradiation. CONCLUSION: In this mouse model, PHY906 (KD018) decreased the toxicity of abdominal irradiation without protecting tumors and thereby increased the therapeutic ratio.

Community-university partnerships in community-based research.

PROBLEM: Community-engaged research (CEnR) is a complex, collaborative process that presents many challenges and requires investment of time and commitment by both community and university research partners. PURPOSE: This paper describes the experience of a group of university and community members developing a set of guidelines for the ethical conduct of CEnR projects. KEY POINTS: The paper outlines the process of guideline development and lessons learned from this collaborative effort, which was based upon approaches and methods of community-based participatory research (CBPR). CONCLUSIONS: The guidelines are included and may serve as a framework to be individualized by other partnerships. Our experience shows that the very process of review, revision, and engagement is extremely helpful in creating a framework that works for the specific communities and for establishing working relationships among the partners so that all stakeholders feel ownership and investment in the framework and the collaborative research efforts.

Targeting cancer with a lupus autoantibody.

Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored. We report the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair-deficient malignancies. We find that 3E10 preferentially binds DNA single-strand tails, inhibits key steps in DNA single-strand and double-strand break repair, and sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging therapy, including doxorubicin and radiation. Moreover, we demonstrate that 3E10 alone is synthetically lethal to BRCA2-deficient human cancer cells and selectively sensitizes such cells to low-dose doxorubicin. Our results establish an approach to cancer therapy that we expect will be particularly applicable to BRCA2-related malignancies such as breast, ovarian, and prostate cancers. In addition, our findings raise the possibility that lupus autoantibodies may be partly responsible for the intrinsic deficiencies in DNA repair and the unexpectedly low rates of breast, ovarian, and prostate cancers observed in SLE patients. In summary, this study provides the basis for the potential use of a lupus anti-DNA antibody in cancer therapy and identifies lupus autoantibodies as a potentially rich source of therapeutic agents.

Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and in vivo.

Agents with selective toxicity to hypoxic cells have shown promise as adjuncts to radiotherapy. Our previous studies showed that the bioreductive alkylating agent KS119 had an extremely large differential toxicity to severely hypoxic and aerobic cells in cell culture, and was effective in killing the hypoxic cells of EMT6 mouse mammary tumors in vivo. However, the limited solubility of that compound precluded its development as an anticancer drug. Here we report our initial studies with KS119W, a water-soluble analog of KS119. The cytotoxicity of KS119W to EMT6 cells in vitro was similar to that of KS119, with both agents producing only minimal cytotoxicity to aerobic cells even after intensive treatments, while producing pronounced cytotoxicity to oxygen-deficient cells. This resulted in large differentials in the toxicities to hypoxic and aerobic cells (>1,000-fold at 10 µM). Low pH had only minimal effects on the cytotoxicity of KS119W. Under hypoxic conditions, EMT6 cells transfected to express high levels of either human or mouse versions of the repair protein O(6)-alkylguanine-DNA alkyltransferase, which is also known as O(6)-methylguanine DNA-methyltransferase, were much more resistant to KS119W than parental EMT6 cells lacking O(6)-alkylguanine-DNA alkyltransferase, confirming the importance of DNA O-6-alkylation to the cytotoxicity of this agent. Studies with EMT6 tumors in BALB/c Rw mice using both tumor cell survival and tumor growth delay assays showed that KS119W was effective as an adjunct to irradiation for the treatment of solid tumors in vivo, producing additive or supra-additive effects in most combination regimens for which the interactions could be evaluated. Our findings encourage additional preclinical studies to examine further the antineoplastic effects of KS119W alone and in combination with radiation, and to examine the pharmacology and toxicology of this new bioreductive alkylating agent so that its potential for clinical use as an adjuvant to radiotherapy can be evaluated.

Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies.

Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research.

Broadcasting in the airways: the fifth anniversary of the Radiation Research Podcast (1).

The Radiation Research Podcast was funded just over five years ago by a few Radiation Research Society members. To date, the volunteers running the podcast have produced and published online, open access, over 70 audio interviews. The program includes monthly interviews with authors of articles, award winners, and other recordings at conferences, such as round table discussions. We here present an overview of the podcast, from its creation to its fifth birthday, to explain how it is working, how the featured interviews are scheduled, and what future directions are taken. So, stay tuned!

Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors.

PURPOSE: These studies explored questions related to the potential use of Laromustine in the treatment of solid tumors and in combination with radiotherapy. MATERIALS AND METHODS: The studies used mouse EMT6 cells (both parental and transfected with genes for O(6)-alkylguanine-DNA transferase [AGT]), repair-deficient human Fanconi Anemia C and Chinese hamster VC8 (BRCA2(-/-)) cells and corresponding control cells, and EMT6 tumors in mice assayed using cell survival and tumor growth assays. RESULTS: Hypoxia during Laromustine treatment did not protect EMT6 cells or human fibroblasts from this agent. Rapidly proliferating EMT6 cells were more sensitive than quiescent cultures. EMT6 cells expressing mouse or human AGT, which removes O(6)-alkyl groups from DNA guanine, thereby protecting against G-C crosslink formation, increased resistance to Laromustine. Crosslink-repair-deficient Fanconi Anemia C and VC8 cells were hypersensitive to Laromustine, confirming the importance of crosslinks as lethal lesions. In vitro, Laromustine and radiation produced additive toxicities to EMT6 cells. Studies using tumor cell survival and tumor growth assays showed effects of regimens combining Laromustine and radiation that were compatible with additive or subadditive interactions. CONCLUSIONS: The effects of Laromustine on solid tumors and with radiation are complex and are influenced by microenvironmental and proliferative heterogeneity within these malignancies.

Subclinical vitamin A deficiency does not increase development of tumors in irradiated or unirradiated lungs.

Cancer patients often have subclinical vitamin A deficiencies and low vitamin A lung levels. Previous studies showed that subclinical vitamin A deficiency increased the severity of pneumonitis induced by whole-lung irradiation in rats. Many studies have shown that lung irradiation increases the number of lung tumors developing from intravenously injected tumor cells in mice. We examined the impact of vitamin A deficiency on the development of lung metastases from a highly metastatic syngeneic rat rhabdomyosarcoma in normal rats and rats receiving prior lung irradiation. Weanling female WAGrijY rats were randomized to receive either a diet lacking both vitamin A and beta-carotene or a control diet. After five weeks, the deficient diet significantly decreased levels of retinol in the lung and liver but not in the serum, modeling the tissue and blood levels seen in prior studies of patients with subclinical vitamin A inadequacy. The vitamin A-deficient diet did not alter the number of lung tumors developing from intravenously injected tumor cells in unirradiated rats. Whole-lung irradiation produced dose-dependent increases in the number of lung tumors developing from tumor cells injected intravenously one or 29 d after irradiation. Vitamin A deficiency did not alter these dose-response curves, indicating that the more intense radiation-induced pneumonitis seen previously in vitamin A-deficient rats did not alter the enhancement of metastases produced by whole-lung irradiation. Moreover, inadequate vitamin A intake did not influence the growth of tumors implanted subcutaneously or increase the number or size of the spontaneous lung metastases developing from these subcutaneous tumors. Thus, although low vitamin A status influences the development of lung injury and is considered a possible modifiable risk factor increasing risk of primary cancer, it did not affect the growth of subcutaneous tumors or increase the development of artificial or spontaneous lung metastases in this rat model.

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers.

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the (131)Cs, (125)I and (103)Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using (125)I sources was less affected by edema than PIB using (131)Cs or (103)Pd sources due to the long radioactive decay half-life of (125)I. The effect of edema on PIB using (131)Cs or (103)Pd was similar. The effect of edema on (103)Pd PIB was slightly greater, even though the decay half-life of (103)Pd (17 days) is longer than that of (131)Cs (9.7 days), because the advantage of the longer (103)Pd decay half-life was negated by the lower effective energy of the photons it emits (∼21 keV compared to ∼30.4 keV for (131)Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/ß ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

Spontaneous coagulopathy in inbred WAG/RijYcb rats.

Here we describe a series of cases of spontaneous coagulopathy in a colony of inbred WAG/RijYcb (WAG/RijY) rats. This strain previously had been bred at our institution without symptomatology for several decades. The index case was a 10-wk-old male rat that developed a large hematoma at a subcutaneous injection site. Clinicopathologic findings included a decreased RBC count, decreased hematocrit, decreased hemoglobin concentration, normal PT, and prolonged (50% to 70%) aPTT (52 s; reference, 15 to 33 s). Examination of additional WAG/RijY rats that died unexpectedly or had clinical signs of bleeding in the absence of experimental manipulation also revealed normal PT and prolonged aPTT. Histologic examinations of tissues from all rats were unremarkable except for severe acute focally extensive hemorrhage corresponding to the macroscopic findings of acute hemorrhage. Furthermore the aPTT in 8 clinically normal adult rats and 8 clinically normal 4-wk-old WAG/RijY littermates of both sexes was prolonged. We conclude that these WAG/RijY rats have an inherited defect in the intrinsic coagulation pathway.

Aplidin as a potential adjunct to radiation therapy: in vitro studies.

PURPOSE: Aplidin (plitidespin) is a novel cyclic depsipeptide, currently in Phase II clinical trials for solid and hematologic malignancies. We examined the effects of oxygen on the cytotoxicity of Aplidin and the interactions between Aplidin and radiation. These factors will be important if Aplidin is used clinically in combination with radiotherapy. MATERIALS: Exponentially-growing EMT6 mouse mammary tumour cells in monolayer cultures were treated with Aplidin and 250 kV X-rays. RESULTS: The cytotoxicity of Aplidin was not altered either by incubation in moderate hypoxia before and during a 24 h drug treatment or by incubation in severe hypoxia before and during a 2 h drug treatment. Treatment with Aplidin plus radiation produced cytotoxicities compatible with additive or supraadditive cytotoxicities. Cells treated with 1 microM Aplidin for 24 h then killed by 100 Gy of radiation were toxic to untreated cells co-cultured with them. CONCLUSIONS: The cytotoxicity of Aplidin is independent of the oxygenation during treatment. Aplidin, or an active metabolite of Aplidin, is retained in the cells and later released as the radiation-sterilised cells die, producing a Bystander effect that kills neighbouring cells. This Bystander effect could affect the outcome of therapeutic regimens combining Aplidin and radiation.

American Society for Radiation Oncology (ASTRO) survey of radiation biology educators in U.S. and Canadian radiation oncology residency programs.

PURPOSE: To obtain, in a survey-based study, detailed information on the faculty currently responsible for teaching radiation biology courses to radiation oncology residents in the United States and Canada. METHODS AND MATERIALS: In March-December 2007 a survey questionnaire was sent to faculty having primary responsibility for teaching radiation biology to residents in 93 radiation oncology residency programs in the United States and Canada. RESULTS: The responses to this survey document the aging of the faculty who have primary responsibility for teaching radiation biology to radiation oncology residents. The survey found a dramatic decline with time in the percentage of educators whose graduate training was in radiation biology. A significant number of the educators responsible for teaching radiation biology were not fully acquainted with the radiation sciences, either through training or practical application. In addition, many were unfamiliar with some of the organizations setting policies and requirements for resident education. Freely available tools, such as the American Society for Radiation Oncology (ASTRO) Radiation and Cancer Biology Practice Examination and Study Guides, were widely used by residents and educators. Consolidation of resident courses or use of a national radiation biology review course was viewed as unlikely by most programs. CONCLUSIONS: A high priority should be given to the development of comprehensive teaching tools to assist those individuals who have responsibility for teaching radiation biology courses but who do not have an extensive background in critical areas of radiobiology related to radiation oncology. These findings also suggest a need for new graduate programs in radiobiology.

Hypoxia and radiation therapy: past history, ongoing research, and future promise.

Tumor hypoxia influences the outcome of treatment with radiotherapy, chemotherapy and even surgery, not only for the treatment of large bulky tumors with extensive necrosis, but also in the treatment of very small primary tumors and recurrences, micrometastases, and surgical margins with microscopic tumor involvement. Because hypoxic tumor cells are resistant to radiation and to many anticancer drugs, many approaches to circumventing the therapeutic resistance induced by hypoxia have been examined in laboratory studies and clinical trials. In this review, these approaches and the results of past laboratory and clinical studies are described and the limitations of the past agents and their testing are discussed. We describe the importance of new technologies for measuring hypoxia in human tumors, which allow assessment of pretreatment tumor oxygen levels and changes in hypoxia over the course of prolonged treatment regimens. These offer the possibility of improving the design of clinical trials and the selection of patients who will benefit from hypoxia-directed therapies, as well as the possibility of facilitating the development of better agents and regimens for use in hypoxia-directed therapy. We also discuss how the improved understanding of the abnormal vascular beds in solid tumors and of the effects of hypoxia and related microenvironmental insults, resulting from recent and ongoing research, offers the potential for finding new therapeutic targets, that may lead to the development of new agents and novel therapeutic approaches for selectively targeting cells in the adverse microenvironments within solid tumors.

The FDP Faculty Burden Survey.

To better understand the administrative burdens placed on faculty who perform research, the Faculty Standing Committee of the Federal Demonstration Partnership (FDP) invited 23,325 full-time faculty members who were Principal Investigators (PI) or Co-Principal Investigators (Co-PI) on active federally funded research grants to participate in a web-based survey that contained questions on the nature, size, and impact of the administrative tasks associated with their research projects. The responses of the 6,081 faculty respondents show that the administrative burden on faculty is very significant: 42% of the time spent by an average PI on a federally funded research project was reported to be expended on administrative tasks related to that project rather than on research. This administrative burden does not stem from one or a few exceptionally onerous tasks, but instead reflects the cumulative effect of the many administrative burdens imposed by different funding agencies, different offices within agencies, auditing and accrediting agencies, and academic institutions. The lack of institutional assistance contributes to the administrative workload of the faculty. Many burdens are remarkably constant across funding agencies, universities, disciplines, and faculty subgroups. The report documents the negative effect reported for these administrative burdens on the productivity of researchers, the careers of young faculty members, and the training of students.